The Effect of <i>Yokukansan</i>, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug–Metabolizing Enzyme Activities in Healthy Male Volunteers

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  • Soraoka Hiromi
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Oniki Kentaro
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Matsuda Kazuki
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Ono Tatsumasa
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Taharazako Kosuke
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Uchiyashiki Yoshihiro
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Kamihashi Ryoko
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Kita Ayana
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Takashima Ayaka
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Nakagawa Kazuko
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University Center for Clinical Pharmaceutical Sciences, Kumamoto University
  • Yasui-Furukori Norio
    Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University
  • Kadowaki Daisuke
    Center for Clinical Pharmaceutical Sciences, Kumamoto University Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University
  • Miyata Keishi
    Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University
  • Saruwatari Junji
    Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University Center for Clinical Pharmaceutical Sciences, Kumamoto University

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  • The Effect of Yokukansan, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug-Metabolizing Enzyme Activities in Healthy Male Volunteers

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<p>The concomitant use of herb and prescription medications is increasing globally. Herb–drug interactions are therefore a clinically important problem. Yokukansan (YKS), a Japanese traditional herbal medicine, is one of the most frequently used herbal medicines. It is effective for treating the behavioral and psychological symptoms of dementia. We investigated the potential effects of YKS on drug–metabolizing enzyme activities in humans. An open-label repeat-dose study was conducted in 26 healthy Japanese male volunteers (age: 22.7±2.3 years) with no history of smoking. An 8-h urine sample was collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan before and after the administration of YKS (2.5 g, twice a day for 1 week). The activities of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) were assessed based on the urinary metabolic indices of caffeine and dextromethorphan, and the urinary excretion ratio of 6β-hydroxycortisol to cortisol. There were no statistically significant differences in the activities of the examined enzymes before or after the 7-d administration of YKS. Although further studies assessing the influence of YKS on the pharmacokinetics and pharmacodynamics of the substrates of the drug–metabolizing enzymes are needed to verify the present results, YKS is unlikely that a pharmacokinetic interaction will occur with concomitantly administered medications that are predominantly metabolized by the CYP1A2, CYP2D6, CYP3A, XO and NAT2.</p>

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